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Myogenic Potential of Muscle Side and Main Population Cells after Intravenous Injection into Sub-lethally Irradiated mdx Mice

Kristina R. Muskiewicz, Natasha Y. Frank, Alan F. Flint and Emanuela Gussoni

Division of Genetics and Program in Genomics, Children's Hospital, Boston, Massachusetts

Correspondence to: Emanuela Gussoni, Division of Genetics, Program in Genomics, Children's Hospital Boston, 320 Longwood Avenue, Boston, MA 02115. E-mail: gussoni{at}enders.tch.harvard.edu

Muscle side population (SP) cells have demonstrated hematopoietic and myogenic activities in vivo upon intravenous (IV) injection into lethally irradiated mdx mice. In contrast, muscle main population (MP) cells were unable to rescue the bone marrow of lethally irradiated mice and, consequently, their in vivo myogenic potential could not be assessed using this method. In the current study, muscle SP or MP cells derived from syngeneic wild-type male mice were delivered to sub-lethally irradiated mdx female mice by single or serial IV injections. Recipient mice were euthanized 12 weeks after transplantation at which time the quadriceps and diaphragm muscles were analyzed for the presence of donor-derived cells. Mice injected with 10⁴ muscle SP cells or with 10⁶ MP cells appeared to have similar numbers of dystrophin-positive myofibers containing fused donor nuclei. Analysis of the remaining tissue via real-time quantitative PCR indicated that mice injected with muscle SP cells had a higher percentage of donor-derived Y-DNA in the quadriceps than mice injected with MP cells, suggesting that muscle SP cells may be enriched for progenitors able to engraft dystrophic skeletal muscles from the circulation. Although the overall engraftment did not reach therapeutically significant levels, these results indicate that further optimization of cell delivery techniques may lead to improved efficacy of cell-mediated therapy using muscle SP cells. (J Histochem Cytochem 53:861–873, 2005)

Key Words: muscular dystrophy • cell-based therapy • muscle side population • muscle main population

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